Some science behind the scenes
The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription.
TOR was first discovered in yeast J.N. Heitman, N.R. Movva and M.N. Hall [Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast, Science 253 (1991)]. It was designated as mTOR, the mammalian target of rapamycin. The binding of immunosuppressant drugs like rapamycin and umirolimus to mTOR is thought to block mTOR's crucial role in these cellular events, resulting in arrest of the cell cycle, and ultimately, cell proliferation.
We can thus see that any drug within this category has a role in suppressing cancer cells and indeed many of the drugs are used in chemotherapy not in suppressing the immune system at all – it depends on where they are targeted.
I will provide the description of how it works, but it will probably remain a mystery to you even after the explanation [as it did to me]!
“Drugs in this category inhibit cell proliferation by actions which occur downstream of growth factor binding. The signal transduction events which culminate in cell cycle arrest in the G1 phase are initiated as a result of ligand binding to an immunophilin known as FK binding protein-12. Subsequent investigations showed that rapamycin binds to this intracellular target, forming an FKBP12–rapamycin complex which is not in itself inhibitory, but does have the capacity to block the integral protein kinase target of rapamycin (TOR)”.
If the mTOR kinase is inhibited, the cell no longer produces the key proteins needed for proliferation, growth, survival, and angiogenesis. This is how it helps in cancer arrest, as cancer cells slow down or are even halted in their out of control proliferation - theoretically. mTOR is activated in tumor cells by various mechanisms including growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes, so the causes aren’t really addressed using these drugs, only the effects.
When used as immunosuppressants, they have a similar suppressive effect but not on the immune system. Sirolimus, for example, inhibits the response to interleukin-2 (IL-2), and thereby blocks activation of T- and B-cells. In contrast, an immunosuppressant such as tacrolimus inhibits the production of IL-2. So all the drugs within this category work at the cell level in theory – the T cells and so on are produced as normal, but instead the cell itself is forced to slow down its response to the T cells – it is as if everything in the cell had been put in slow motion.
There are complications that arise with the use of these class of drugs in kidney and lung transplants. Since all the drugs in this class slow down the cell healing process to prevent rejection its use can decrease renal function and can also impair wound healing. Furthermore people who have undergone lung transplants may also find themselves with interstitial pneumonitis – cough fever and difficulty breathing.
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